1. Evaluation of Liver Disease in older children and adolescents
Dr Juliana Muiva-Gitobu
KPA ASC, Mombasa, Kenya
April 2019

2. Outline Case presentation Liver functions
Overview of liver disease in infancy and older children
Specific illnesses reviewed
Conclusion

3. Patient I.A.
15 year with history of progressive and generalized body weakness and swelling of the lower limbs and abdomen over the last 1 year
O/E: FGC. Oedema+, mild pallor, abdominal distension with ascites and hepatomegally
What are his possible differential diagnoses?
What workup would you like to do?

4. Liver Functions Revision
Uptake and processing of nutrients from the intestinal tract
Synthesis and biotransformation of proteins, carbohydrates and lipids
Excretion of bile and hydrophobic compounds
Regulation of energy metabolism
Endocrine functions
Imunological
Drug metabolism
Fluid balance

5. Liver Disease in Infants
Anatomic : Biliary atresia, Choledochal cyst
Infectious : TORCHes
Metabolic : galactosemia
Autoimmune : neonatal sclerosing cholangitis
Vascular : CCF, constrictive pericarditis
Toxic/Drug induced : PNALD

6. Spectrum of Liver Disease in older children
Anatomic
Infectious
Metabolic
Autoimmune
Vascular
Toxic/Drug induced

7. Anatomic Intra-Hepatic Bile Duct diseases (Ductal Plate Malformation):
Congenital Hepatic Fibrosis
Caroli’s Disease and Syndrome
Autosomal Dominant Polycystic Kidney Disease
Extra-Hepatic Bile Duct Diseases
Choledochal Cysts

8. Non Alcoholic Liver Disease
Infectious
Metabolic
Hepatitis B
Hepatitis A
Wilson’s Disease
Hemochromatosis
Non Alcoholic Liver Disease

9. Autoimmune Hepatitis ASC Haemangioma Portal Hypertension
Vascular disorders
Autoimmune Liver Disease
Autoimmune Hepatitis
ASC
Haemangioma
Portal Hypertension

10. Toxic & Drug Induced Liver Disease
Toxic e.g. Aflatoxin
Drug induced
Dose Dependent
Idiosyncratic

11. Disorders of Ductal Plate Malformation

12. Disorders of Ductal Plate Malformation
Can present with hepatomegally or can be incidental finding
Features of portal hypertension
Liver Functions may/may not be deranged
Radiology important: Ultrasound, MRI
Management guided by management of underlying disease and associated complications e.g renal disease
Surgical intervention esp for choledochal cyst, prevent biliary cirrhosis

13. Hepatitis B Persistent HBsAg positive >6/12
>360 million persons infected worldwide
Majority of childhood infections in vertical or horizontal transmission
Risk of chronicity
90% newborn
20-30% <5 years
<5% adults
Majority are asymptomatic. Some with malaise, anorexia, abdominal discomfort, then jaundice. 1% of acute infections may have severe presentation

14. Stages of Hepatitis B infection

15. Treatment Strategies Hepatitis B

16. Hepatitis A RNA virus, fecal-oral transmission
Majority of infections asymptomatic, up to 1.5 million cases annually
Clinically presents with anorexia, nausea, malaise, fever, abdominal pain, diarrhoea and vomiting
1% with severe presentation, % mortality, especially with fulminant hepatic failure. Relapses possible

17. Hepatitis A Diagnosis: Ultrasound and liver biopsy not routine
Clinical features
ALT> x10 ULN, or 400
ELISA anti-HAV IgM
Ultrasound and liver biopsy not routine

18. Wilson’s disease
Copper: essential co-factor for several proteins; useful in neurological signalling and RBC formation.
Wilson’s disease: impaired excretion of Cu →Accumulation of Cu in hepatocytes, with eventual spillover to other systems
Defective gene ATP7B →defective protein →Decreased Cu excretion & defective caeruplasmin formation

19. Clinical features

20. Diagnosis of Wilson’s Disease

21. Treatment of Wilson’s Disease
Reduce copper intake
Increase copper excretion: D-penicillamine, Trientine
Reduce copper absorption: Zinc acetate
Liver Transplantation

22. Autoimmune Hepatitis Disease characterised by
Histologically:Dense mononuclear cell infiltrate in portal tracts
Serology: Hypergammaglobulinemia, Autoantibodies
Chemically: elevated transaminases
3 Types
autoimmune hepatitis
autoimmune sclerosing cholangitis 
de novo autoimmune hepatitis after liver transplantation

23. Clinical Features Affects predominantly females
Divided into 2 types based on antibody profiles
Type 1 
positive for ANA and/or anti-smooth muscle antibodies
Type 2 
positive for anti-Liver/Kidney microsomal antibody type 1
median age of 10 years in type 1 and 7.4 years in type 2
Can present with fulminant hepatic failure in 10%, Portal hypertension +/- GI bleeding, or can be asymptomatic
Type 2 associated with other AI disorders e.g. IDDM, Thyroiditis and IBD

24. Diagnosis LFTs: Serology: raised AST and ALT
normal or mildly raised GGT and ALP
Variable bilirubin
Low Albumin
abnormal INR
Serology:
ANA, ASM, ALKM
titres of 1/20 for ANA/SMA and 1/10 for anti-LKM-1 are significant
Hypergammaglobulinemia, largely IgG

25. Diagnosis Histology: Imaging: US, MRCP (ASC)
dense mononuclear and plasma cell infiltration of the portal areas which expands into the liver lobule
Destruction of hepatocytes at the periphery of the lobule with erosion of the limiting plate (interface hepatitis)
Connective tissue collapse due to hepatocyte death expanding from portal area into lobule (bridging collapse)
Hepatic regeneration with 'rosette' formation
Cirrhosis
Imaging: US, MRCP (ASC)

26. Treatment Prednisone 2mg/kg/day (max 40mg) Azathioprine 0.5mg/kg/day
Monitor Rx response on LFTs and TBC
Manage complications e.g. portal hypertension

27. Portal Hypertension
Liver supplied by both the portal vein (75%) and the hepatic artery (25%)
Pressure between portal and hepatic venous systems <5mmHg
PH is defined as a portal pressure greater than 10 mmHg or a gradient greater than 4 mmHg.

28. Portal Hypertension Aetiology can be classified as Prehepatic
Intrahepatic (Presinusoidal, sinusoidal and postsinusoidal)
Posthepatic
Peripherally other complications develop:
Peripheral and splanchnic vasodilation
Increased cardiac output
Shunting
Salt and water retention by kidneys, etc

29. Portal Hypertension
Clinically most present with ascites, gastrointestinal hemorrhage, and splenomegally
Laboratory workup includes LFTs, blood cell and platelet count, and coagulation. Investigations targeted at underlying liver disease
Radiology
Portal vein doppler studies
Triple phase CT scan
MR angiography

30. Portal Hypertension Management Ascites: Diuretics, low salt diet
Variceal bleeding: endoscopy and VBL, Prophylaxis with beta blocker
Surgical procedures: TIPS, Rex shunt, etc

31. Patient I.A. 1. Thyroid profile – within normal limits
Results:
1. Thyroid profile – within normal limits
2. Alpha Fetoprotein – 2.4 iu/ml
3. Hepatitis A IgM, Hepatitis C antibody, Hepatitis B surface antigen- Negative
4. CMV IgM – Negative
5. Ferritin – ng/mL
6. ANA - Negative
7. Anti ds DNA – Negative
8. Caeruloplasmin – 24.5 mg/dL
9. Anti-smooth muscle antibodies – Positive
10. Anti-liver kidney murosomal antibodies – Negative
11. CT Scan abdomen – Liver Cirrhosis with splenomegaly
12. Liver biopsy- not possible, elevated INR

32. Patient I.A.
Started on Prednisone nad Azathioprine with little improvement.
Later results were as follows:
Urine copper excretion – ug/24hr
After Penicillamine challenge – ug/24hr
I.A. started on penicillamine with significant improvement

33. Conclusion Liver disease in older children has a different aetiology
Many diseases may present without jaundice
Diagnosis is possible with a variety of tests, most of which can be done in the majority of facilities in this country.