CLD sec to Autoimmune Hepatitis Type 1.pptx

Very good presentation

1. PROBLEM CASE DR. SOOBIA AKHTAR FCPS PART II TRAINEE MEDICAL UNIT 3

2. 6 yrs old male child SHUJA ,weighing 17 kg resident of Karachi came to OPD on 23 July 2015 with complaints of : Jaundice ......... 1 month Pallor …….. 1 month Abdominal distension …….. 15 days Abdominal pain …….. 2 days

3. HOPC

4. Antenatal History Booked case Regular visits U/S scan done Took M/V and F/A Received TT Mother was diagnosed as Hep C + ve on ELISA during antenatal visits at 6 th month of gestation HCV RNA positive on PCR done after 1 year 6 month .

5. Family History He is 3 rd issue of consanguineous marriage 3 siblings all are alive and healthy Father has vitiligo (from 17 years of age ) No family h/o D.M , arthralgia , arthritis and any bowel disease Mother was Hep C positive for which she had been treated

6. Drug Hx Dietary Hx Immunization Hx Developmental Hx

7. General Physical Examination Pale looking child lying on bed. Vitals HR 104 b / min RR 26 br / min Temp 98 F BP 100/65 mmHg (b/w 50 th to 90 th percentile )

8. Severe pallor , jaundice + No edema , clubbing , palmar e rythema , koilonychia , cyanosis, petechiae , bruises or lymphadenopathy No flapping tremors , spider nevi, itch marks No rash and joint swelling

9. Anthropometric measures Wt: 17 kg ( 10 th percentile ) Ht: 100 cm ( 3rd percentile)

10. Abdominal exam: distended with prominent veins , umblicus everted non tender Liver : Liver palpable 4 cm below right costal margin in mid clavicular line, firm in consistency with regular margins smooth surface & total liver span of 12 cm Spleen : Palpable 2 cm below left costal margin in its long axis. Fluid thrill and Shifting Dullness : negative Gut sound: audible

11. Chest : unremarkable CNS: intact CVS: S1 + S2 +0 Musculoskeletal: Normal

12. Differential Diagnosis Acute Hepatitis on chronic liver disease Wilson’s disease Autoimmune hepatitis Viral hepatitis ( Hep B or Hep C )

13. I nvestigations CBC CBC 16-7-15 23-7-15 25-7-15 11-8-15 Hb 5.1 5.0 6.1 7.3 MCV 65.5 64.7 68.8 65 MCH 17.2 17.1 19.6 19 HCT 19.4 18.9 21.4 25 WBC 5.8 8.0 47 6.6 N 38 43 52 50 L 56 52 52 45 Plat 138 178 135 211 ESR 20 Retics 1.2 Corrected retics 0.64

14. LFTs 14-7-15 16-7-15 23-7-15 10-8-15 (AKU) 8-9-15 T.B 0.8 1.2 2.8 1.8 1.5 D.B 0.2 0.4 2.1 1.4 0.59 SGPT 117 140 182 256 67 SGOT 713 GGT ALK PO4 542 584 530 430 465 Total protein 7.3 Albumin 1.9 2.5 Globulin 5.4 A/G ratio 0.35 ALP/ALT Ratio 4.6 4.1 2.9 1.6 6.9

15. UCE 16-7-15 23-7-15 Na 135 137 K 5.0 4.5 Cl 100 111 Urea 17 18 Creatinine 0.4 0.5

16. PT & aPTT PT C = 14 sec T = 23 sec aPTT C = 34 sec T = 34 sec

17. Ultrasound Abdomen Liver 11cm in size, coarse texture & regular margins Portal vein 0.6 cm patent with normal flow Spleen 8.9 cm enlarged No ascites Thick walled GB with a wall thickness of 0.7 cm

18. VIRAL PROFILE Test Value Cut off value Result HCV Antibody 0.203 0.650 Non reactive HBsAg 0.54 1.00 Non reactive Hepatitis A antibody IgM 0.035 0.130 Non reactive Hepatitis E virus Antibody IgG IgM 0.056 0.180 0.398 0.180 Negative Negative

19. WORK UP FOR WILSON DISEASE Serum ceruloplasmin …… 0.21 G /L (4-12 years : 0.25 -0.45 G/L) 24 hr urinary copper…….9 ug /day (normal value 60 ug /day) ( Wilson’s disease >200 ug /day) KF ring …….. negative

20. Work Up For Autoimmune Hepatitis Direct Coomb’s Positive IgG level 44.07 ( 6.5 – 16 ) ANA Positive, homogenous ASMA Negative AMA Negative Anti LKMA Negative (1.1)

21. Final Diagnosis CLD sec to Autoimmune Hepatitis Type 1

22. Management Admitted in ward Basic work up sent Antibiotic Inj Vit K 5 mg I/V od for 3 days Inj Zantac 15 mg I/V bd Multivitamins ( Vit D, A, E ) Tab Deltacortil 2 tab tds (started from 10 aug 2015 )

23. Discussion

24. Chronic liver disease Duration of liver disease (typically >3-6 mo) or by evidence of chronic hepatic decompensation ( hypoalbuminemia , thrombocytopenia) or physical stigmata of chronic liver disease (clubbing, spider telangiectasia , hepatosplenomegaly ).

25. CAUSES OF CHRONIC HEPATITIS CHRONIC VIRAL HEPATITIS Hep C Hep D Hep B AUTOIMMUNE HEPATITIS Antibody positive Antiactin Anti-liver-kidney microsomal antibody positive Antisoluble liver antigen antibody positive Overlap(includes antibody to liver specific lipoprotein or asialoglycoprotein ) Overlap syndrome with sclerosing cholangitis and autoantibodies Systemic lupus erythematosus Celiac disease

26. DRUG INDUCED HEPATITIS Isoniazid Methyldopa Sulfonamid Dantrolene Nitrofurontine

27. METABOLIC DISORDERS ASSOCIATED WITH CHRONIC LIVER DISEASE Wilson disease Alpha 1 antitrypsin deficiency Tyrosinemia Niemann -pick disease type 2 Glycogen storage disease type 4 Cystic fibrosis Galactosemia NON ALCHOLIC STETOHEPATITIS (OBESITY & INSULIN RESISTANCE)

28. Autoimmune Hepatitis “Chronic hepatic inflammatory process manifested by elevated serum amino transaminase, liver-associated serum autoantibodies, and/or hypergammaglobulinemia .” The target of the inflammatory process can include hepatocytes and to a lesser extent bile duct epithelium .

29. Chronicity is determined either by Duration of liver disease (typically >3-6 mo) or by evidence of chronic hepatic decompensation hypoalbuminemia , thrombocytopenia) or physical stigmata of chronic liver disease (clubbing, spider telangiectasia , hepatosplenomegaly ). The severity is variable; T he affected child might have only biochemical evidence of liver dysfunction, might have stigmata of chronic liver disease, or can present in hepatic failure.

30. CLASSIFICATION OF AUTOIMMUNE HEPATITIS VARIABLE TYPE 1 AUTOIMMUNE TYPE 2 AUTOIMMUNE HEPATITIS HEPATITIS Characteristic autoantibodies Antinuclear antibody Antibody against liver -kidney microsome 1* Smooth-muscle antibody   Antiactin antibody Antibody against liver cytosol Antibodies against soluble liver antigen &liver pancrease antigen   Atypical perinuclear antineutrophil cytoplasmic antibody   Geographic variation worldwide worldwide Age at presentation Any age predominnantly childhood and young adulthood Sex female 75 % cases female 95% cases Association with other autoimmune diseases common common Clinical severitybroad range   generally severe Histopathologic features at presentation broad range generally advanced Treatment failure infrequent frequent Relapse after drug withdrawl variable common Need for long term maintainance variable 100%

31. CLINICAL MANIFESTATION Most cases have an insidious onset. May be asymptomatic or have nonspecific symptoms ( eg , fatigue, anorexia, weight loss, behavioral changes, amenorrhea) Extrahepatic manifestation (arthritis . vasculitis ,nephritis , coombs + ve anemia and rash) Clinical features of autoimmune hepatitis widely vary.

32. Common findings on physical examination are as follows: Hepatomegaly (83%) Jaundice (69%) Splenomegaly (32%) Spider Nevi (58%) Ascites (20%) Encephalopathy (14%)

33. Complications may include the following: Cirrhosis and complications of cirrhosis ( eg , ascites , coagulopathy , hepatic coma) Portal hypertension Esophageal varices Malnutrition (with poor growth in children)

34. LAB FINDINGS Raised serum aminotransferases (in asymptomatic cases 100-300 IU/L ,>1000 IU/L can be seen in symptomatic pt) Serum bilirubin concentration (predominantly direct fraction) commonly 2-10 mg /dl ALP & GGT are normal to slightly increased Prolonged Prothrombin time Hypoalbuminemia Hypergammaglobinemia Serum IGg usually >16 g/dl Autoantibody ANA ,ASMA ,LKMA ,PANCA

35. MANAGEMENT PREDNISOLONE 1-2 mg /kg continue until amintransferase values returns to less than twice the upperlimit of normal Dose should then be tapered in 5mg decrements over 2-4 month until maintenance dose of 0.1 -0.3 mg /kg /24hr achieved

36. AZATHIOPRINE (1.5 -2 mg /kg/24 hr,up to 100mg /24 hr) or 6 MERCAPTOPURINE 1 – 1.5 mg /kg/24 hr ) can be added in pt who respond poorly,experience severe side effects or who can not maintained on low dose steroids Cases Refractory to standard therapy : BUDESONIDE ,CYCLOSPORINE,TACROLIMUS ,MYCOPHENYLATE MOFETILE

37. THANKS