Evaluation of Liver Disease in older children and adolescents

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

9. Autoimmune Liver Disease Vascular disorders • 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 espfor 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, 0.2-0.4% mortality, especially with fulminant hepatic failure. Relapses possible

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

25. Diagnosis • Histology: • 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. 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 – 22.49 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 – 109.85ug/24hr • After Penicillamine challenge – 446.96ug/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.